Selinexor, Cyclophosphamide and Prednisone in Myeloma

Inclusion Criteria

• •1. Able to give informed consent and willing to follow all trial protocol assessments
• •2. Aged 18 years or over
• •3. Participants with confirmed myeloma based on International Myeloma Working Group (IMWG) criteria (Rajkumar et al. (2014))
• •4. Measurable disease with at least one of the following:
• •* Paraprotein ≥5g/L
• •* Serum free light chains ≥100mg/L with abnormal ratio for light chain only myeloma
• •* Bence Jones protein ≥200mg/L
• •5. Participants with relapsed or relapsed refractory myeloma who have received ≥ 2 prior anti-myeloma treatments including a proteasome inhibitor and lenalidomide, and now require further treatment
• •6. Patients for which cyclophosphamide and prednisone alone would be a suitable treatment
• •7. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• •8. Female participants of childbearing potential must agree to use two methods of contraception (including one highly effective and one effective method of contraception) and have a negative urine pregnancy test at screening.
• •Male participants must use an effective barrier method of contraception if sexually active with a female of childbearing potential.
• •For both male and female participants, effective methods of contraception must be used throughout the trial and for at least 36 months following the last dose of trial treatment
• •9. Required laboratory values within 14 days prior to randomisation:
• •* Platelet count ≥50x109/L. Platelet count of 30-50 is acceptable if bone marrow aspirate or trephine shows tumour replacement of \>50%. Platelet support is permitted within 14 days prior to randomisation, although platelet transfusions to help participants meet eligibility criteria are not allowed within 72 hours prior to the blood sample to confirm protocol eligibility
• •* Absolute neutrophil count ≥1.0 x 109/L. Growth factor support is not permitted within 14 days prior to randomisation
• •* Haemoglobin ≥ 8090 g/L. Blood support is permitted
• •* Alanine transaminase (ALT) and / or aspartate transaminase (AST) ≤3 x upper limit of normal
• •* Creatinine clearance ≥ 2030 ml/min (using Cockcroft Gault formula)
• •* Bilirubin ≤1.5 x upper limit of normal . Gilberts syndrome patients must have a total bilirubin ≤3 x upper limit of normal
• •1. Randomised to CP on the MUKtwelve trial, has tolerated treatment and can continue on CP during the SCP treatment, and received at least one full cycle of treatment
• •2. Centrally confirmed disease progression by IMWG criteria. This must be confirmed by two consecutive assessments based on local lab results. Local laboratory reports must be sent to CTRU to confirm progression and site must have received confirmation of progression from CTRU.
• •3. ECOG performance status ≤2
• •4. Required laboratory values within 14 days prior to starting treatment on SCP:
• •* Platelet count ≥50x109/L. Platelet count of 30-50 is acceptable if bone marrow aspirate or trephine shows tumour replacement of \>50%. Platelet support is permitted within 14 days prior to starting SCP, although platelet transfusions to help participants meet eligibility criteria are not allowed within 72 hours prior to the blood sample to confirm protocol eligibility
• •* Absolute neutrophil count ≥1.0 x 109/L.
• •* Haemoglobin ≥ 80 g/L. Blood support is permitted
• •* Alanine transaminase (ALT) and / or aspartate transaminase (AST) ≤3 x upper limit of normal
• •* Creatinine clearance ≥ 20 ml/min (using Cockcroft Gault formula)
• •* Bilirubin ≤1.5 x upper limit of normal. Suspected Gilberts syndrome patients must have a total bilirubin ≤3 x upper limit of normal
• •* B2M
• •5. Female participants of childbearing potential must agree to use two methods of contraception (including one highly effective and one effective method of contraception) and have a negative urine pregnancy test at screening.
• •Male participants must use an effective barrier method of contraception if sexually active with a female of childbearing potential.
• •For both male and female participants, effective methods of contraception must be used throughout the trial and for 12 months following the last dose of trial treatment